Methods for Determining Risk of Developing Regular Smoking Behavior

a risk and smoking behavior technology, applied in the field of human genetic polymorphisms, can solve the problems of affecting the development of regular smoking behavior, the role of high affinity nicotine receptor subunits in human smoking, and the major source of morbidity, mortality and economic loss, so as to and increase the risk of developing regular smoking behavior

Inactive Publication Date: 2009-07-09
WASHINGTON UNIV IN SAINT LOUIS
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Benefits of technology

[0014]In another embodiment of the invention, there is provided a method for determining whether a subject is at risk for developing regular smoking behavior, the method comprising, in a biological sample from the subject, analyzing a polynucleotide sequence to detect the presence or absence of at least one DNA marker in exon/intron 5 region of CHRNA4, wherein the DNA marker is associated with increased risk of developing regular smoking behavior. In one embodiment of the method, the at least one DNA marker comprises at least one SNP selected from the snp 1 T and snp 2 A alleles. In another embodiment of the method, the at least one DNA marker comprises two SNPs consisting of the snp 1 T and sup 2 A alleles.
[0015]In another embodiment of the invention, there is provided a method for detecting the presence or absence in a subject of at least one allelic variant that is associated with increased risk of developing regular smoking behavior, the method comprising detecting the presence or absence of at least one SNP in exon/intron 5 region of CHRNA4, wherein the presence of at least one SNP is associated with increased risk of developing regular smoking behavior. In one embodiment of the method, detecting the presence or absence of at least one SNP comprises detecting the presence or absence of at least one SNP selected from the snp 1 T and snp 2 A alleles. In another embodiment of the method, detecting the presence or absence of at least one SNP comprises detecting the presence or absence of two SNPs consisting of the snp 1 T and snp 2 A alleles.
[0016]In another embodiment of the invention, there is provided a method for detecting in a subject a predisposition to developing regular smoking behavior, comprising, on a CHRNA4 gene obtained from the subject, detecting the presence or absence of an allelic variant of a polymorphic region of exon/intron 5 that is associated with increased risk of developing regular smoking behavior, wherein the polymorphic region comprises SEQ ID NO: 1, and wherein the presence of the allelic variant in the subject is indicative of a predisposition to developing regular smoking behavior in the subject as compared to a subject in which the allelic variant is not present. In one embodiment of the method, the allelic variant comprises a SNP selected from the snp 1 T and snp2A alleles. In another embodiment of the method, the allelic variant comprises two S...

Problems solved by technology

The health consequences of smoking represent a major source of morbidity, mortality and economic loss worldwide.
Despite significant animal evidence for the involvement of the α4 β2 neural nicotinic receptor complex in ...

Method used

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  • Methods for Determining Risk of Developing Regular Smoking Behavior
  • Methods for Determining Risk of Developing Regular Smoking Behavior
  • Methods for Determining Risk of Developing Regular Smoking Behavior

Examples

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example 1

Population-Based Study of Association Between CHRNA4 Polymorphism Status and Regular Smoking

[0056]In order to attempt to link the association of a CHRNA4 polymorphism with inattentive ADHD and the previously described associations of smoking with attention problems, predictors of regular smoking were analyzed in a population-based sample of 1430. Risk for regular smoking was then analyzed for an association with CHRNA4 polymorphism status. As shown in Table 1, the sample consisted of 831 males and 509 females aged 7 to 17 years. The majority of individuals receiving a diagnosis of ADHD by either DSM-IV or latent class criteria (the inattentive and combined subtypes) were males but there was no difference in age or ethnicity by subtype. Consistent with an earlier report (Todd R D, Sitdhiraksa N, Reich W, Ji T H-C, Joyner C A, Neuman R J, Heath A C (2002), Discrimination of DSM-IV and latent class attention deficit / hyperactivity disorder subtypes by educational and cognitive performan...

example 2

Multivariate Logistic Regression Analysis of Association Between CHRNA4 Polymorphism Status and Regular Smoking

[0059]Since smoking is associated with a variety of possible confounding individual characteristics, the magnitude of ADHD predictors of regular smoking was estimated using multivariate logistic regression. Covariates included sex, age, race, zygocity, alcohol abuse, marijuana usage, major depression, oppositional defiant disorder, conduct disorder and ADHD subtype. Due to its high correlation with self-reported smoking, friend's smoking could not be included as a separate covariate. Since these were twin-based data, Huber-White Robust estimators were used to estimate confidence intervals. FIG. 1 shows that though the adjusted odds ratios for prediction of regular smoking were slightly elevated in DSM-IV ADHD subtypes, these were not significant. A significant odds ratio was only found for the inattentive latent class subtype (OR=4.5, 95% CI 1.7-11.8, p=0.003). For this sub...

example 3

Multivariate Logistic Regression Analysis of Association Between CHRNA4 Polymorphism Status and Regular Smoking

[0060]Given that smoking was predicted by latent class ADHD subtype, CHRNA4 genotyping data for the inattentive and combined ADHD subtypes was analyzed to test for association with the presence or absence of smoking. All snp genotype assignments from Todd et al. (Todd R D, Joyner C A, Heath A C, Neuman R J, Reich W (2003), Reliability and stability of a semistructured DSM-IV interview designed for family studies. Journal of the American Academy of Child &Adolescent Psychiatry. 42: 1460-8) were confirmed by genomic DNA sequencing. Analyses were restricted to those individuals who had ever smoked, reducing the sample size from 195 to 76 individuals. As shown in Table 3, there were significant associations of two exon / intron 5 snps with progression to regular smoking when all ADHD individuals were grouped together (OR=2.1, p=0.03 for each). When analyzed separately by combined...

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Abstract

The present invention relates in general to human genetic polymorphisms and their association with human health and to methods and materials for analyzing allelic variations, and to the use of genetic polymorphisms in the diagnosis and treatment of smoking behavior and nicotine dependence. Provided herein are methods for determining risk in a subject of developing regular smoking behavior. Also provided are primers, probes, microarrays, and kits related thereto.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to Provisional Application U.S. Ser. No. 60 / 582,159, filed Jun. 23, 2004.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]Research relating to the invention was supported in part by NIMH grant R01 MH52813, NINDS grant R01 NS 43762 and NIAAA grant R01 AA 13640. The Government has certain rights in the invention.REFERENCE TO A SEQUENCE LISTING[0003]The Sequence Listing, which is a part of the present disclosure, includes a text file comprising nucleotide and / or amino acid sequences of the present invention on a floppy disk. The subject matter of the Sequence Listing is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0004]1. Field of the Invention[0005]The present invention relates in general to human genetic polymorphisms and their association with human health, to methods and materials for analyzing allelic variations, and to the use of genetic polymorphisms ...

Claims

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Application Information

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IPC IPC(8): C12Q1/68C40B40/08
CPCC12Q2600/156C12Q1/6876
Inventor NEUMAN, ROSALINDTODD, RICHARD D.
Owner WASHINGTON UNIV IN SAINT LOUIS
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